Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study

Abstract

VEXAS syndrome (vacuoles in myeloid progenitors, E1 ubiquitin activating enzyme, X-linked, autoinflammatory manifestations and somatic) is an autoinflammatory condition caused by somatically acquired UBA1 mutations. Heiblig et al report on an international retrospective analysis of 30 patients with VEXAS syndrome treated with different Janus kinase (JAK) inhibitors, finding encouraging evidence supporting the use of the JAK1/2 inhibitor ruxolitinib with clinical remissions and reductions in steroid use seen in the majority of patients.

Figure 1.

Antiinflammatory effects of JAKi in patients with VEXAS syndrome. (A) Overall clinical response rates of patients treated with JAKi during 1, 3, or 6 months; results are presented for the whole cohort (left), for patients receiving other JAKi than ruxolitinib (middle), or for patients receiving ruxolitinib (right). (B) Overall biological response rates of patients treated with JAKi during 1, 3, or 6 months; results are presented for the whole cohort (left), for patients receiving other JAKi than ruxolitinib (middle), or for patients receiving ruxolitinib (right).

Figure 2.

Clinical (and hematological) outcome of patients with VEXAS syndrome treated with JAKi. (A) Kaplan-Meier representation of the time to next treatment in patients treated by ruxolitinib or other JAKi. (B) Prednisone dose (percentage of baseline) after 1, 3, and 6 months in patients treated with ruxolitinib or other JAKi. (C-D) Hemoglobin and platelet count evolution at baseline and after 1 and 3 months of ruxolitinib in patients treated with ruxolitinib or other JAKi. (E) UBA1 fish plot of 2 patients treated with ruxolitinib.